Immunotherapy in Non-Small-Cell Lung Cancer (NSCLC).

Treatment of non-small-cell lung cancer depends heavily on the cancer stage, and immunotherapy can play a major role at any stage. For locally advanced stages, the addition of an immune checkpoint inhibitor (ICI) to neoadjuvant chemotherapy improves pathological response and event-free survival. In the adjuvant setting, adding ICI, after adjuvant chemotherapy for resectable cancer, increases the disease-free survival. In unresectable stage III treated with concomitant chemotherapy and radiotherapy, adding ICI as a maintenance therapy increases progression-free survival and overall survival. In the metastatic setting, the addition of ICI to chemotherapy improves overall survival, progression-free survival, and response rates irrespective of the PD-L1 expression. ICI on its own may be considered in cases of PD-L1 expression equal or greater than at least 50%.

BIONIKK: A phase 2 biomarker driven trial with nivolumab and ipilimumab or VEGFR tyrosine kinase inhibitor (TKI) in naïve metastatic kidney cancer.

BACKGROUND: The nivolumab-ipilimumab combination provides an overall response rate of 42% in first-line metastatic treatment of clear cell renal carcinoma (mccRCC). To date, there is no robust predictive biomarker of response to immune checkpoint inhibitor (ICI). In addition, severe autoimmune disorders occur more frequently with ICI combination than with ICI alone. The objective of this study is to compare the efficacy of ICI alone or in combination in patients according to tumor molecular characteristics. METHODS: Using a 35-gene expression mRNA signature, patients were divided into 4 molecular groups (1 to 4). Patients in groups 1 and 4 were randomized to receive nivolumab alone (arms 1A and 4A) or nivolumab plus ipilimumab for 4 injections followed by nivolumab alone (arms 1B and 4B). Patients in groups 2 and 3 were randomized to receive nivolumab plus ipilimumab followed by nivolumab alone (arms 2B and 3B) or a tyrosine kinase inhibitor (sunitinib or pazopanib at the investigator's choice (arms 2C and 3C)). The main objective is the overall response rate by treatment and molecular group. DISCUSSION: BIONIKK is the first trial in mccRCC to study the personalization of treatment with ICI or TKI according to tumor molecular characteristics in mccRCC. This trial is the most appropriate to prospectively identify biomarkers of response to nivolumab used alone or in combination or TKI monotherapy in patients with mccRCC. NCT02960906.

[Third degree atrio-ventricular blockade during a myocarditis occurring under anti-PD1 : Case report and literature review]. / Bloc atrio-ventriculaire de grade III compliquant une myocardite au décours d'un traitement par anti-PD1 : observation d'un cas et revue de la littérature.

INTRODUCTION: Immune Checkpoint Inhibitor (ICI) therapy is now a standard of care in numerous cancers with very promising results. Nevertheless, adverse events, and especially immune-related adverse events (irAEs) not reported during clinical trials, are emerging and can be life-threatening. OBSERVATION: We report here a teachable case of a 80 year-old man, of third-degree atrioventricular block consecutive to myocarditis associated with the administration of nivolumab (anti-PD1) monotherapy. CONCLUSION: Myocarditis occurring during ICI treatment is a rare but potentially lethal event. Daily serum troponin level seems to predict ICI-related myocarditis but interpretation could be difficult in the context of associated myositis. Echocardiography and cardiac MRI are also useful but can remain negative. Electrocardiogram is a cornerstone of myocarditis diagnosis. In case of cardiac involvement, continuous heart rhythm monitoring should be performed in addition to the administration of high-dose corticosteroids therapy and the cessation of ICI therapy. Add-on treatments should be discussed with a well-trained multidisciplinary team.